Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates

Scientific Reports
Yasuha AraiYohei Watanabe

Abstract

The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 2.3.2.1 and clade 2.3.4 strains isolated from 2008-2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new in...Continue Reading

References

Oct 9, 1999·Journal of Virology·E FodorA García-Sastre
Jul 24, 2002·Nucleic Acids Research·Kazutaka KatohTakashi Miyata
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Terrence M TumpeyChristopher F Basler
Dec 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·G GabrielJ Stech
Mar 15, 2006·The Journal of Experimental Medicine·Rachelle SalomonErich Hoffmann
Oct 10, 2007·PLoS Pathogens·Masato HattaYoshihiro Kawaoka
May 6, 2008·Nature Structural & Molecular Biology·Delphine GuilligayStephen Cusack
Sep 13, 2008·Annual Review of Microbiology·Nadia NaffakhSylvie van der Werf
Jan 20, 2011·Nature Communications·Gülsah GabrielHans-Dieter Klenk
Jun 3, 2011·The Journal of General Virology·Yohei WatanabeKazuyoshi Ikuta
Dec 14, 2011·Trends in Microbiology·Yohei WatanabeKazuyoshi Ikuta
Mar 27, 2012·Current Opinion in Virology·Masaki Imai, Yoshihiro Kawaoka
May 3, 2012·Nature Communications·Benjamin MänzMartin Schwemmle
Jun 20, 2012·Emerging Infectious Diseases·Stephanie SonnbergRobert G Webster
Jun 6, 2013·Virus Research·Yi Guan, Gavin J D Smith
Aug 21, 2013·Virus Research·M ImaiY Kawaoka
Mar 4, 2014·The Journal of General Virology·Anna V CauldwellWendy S Barclay
Jun 6, 2014·Journal of Virology·Volker Czudai-MatwichHans-Dieter Klenk
Jul 9, 2014·Clinical and Experimental Vaccine Research·Thanh Hoa Le, Nga Thi Bich Nguyen
Oct 8, 2014·Nature Communications·Shufang FanYoshihiro Kawaoka
Nov 20, 2014·Nature·Alexander PflugStephen Cusack
Nov 25, 2014·Nature Reviews. Microbiology·Amie J EisfeldYoshihiro Kawaoka
Dec 24, 2014·Proceedings of the National Academy of Sciences of the United States of America·Huaiyu TianBing Xu
Dec 6, 2016·Cell Host & Microbe·Yuhai BiGeorge Fu Gao

❮ Previous
Next ❯

Citations

Mar 15, 2019·Emerging Microbes & Infections·Matthijs R A WelkersDirk Eggink

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence microscopy
transfection

Software Mentioned

GraphPad
GraphPad Prism
NIS
Elements

Related Concepts